Immunisation of cattle against Babesia bovis combining a multi-epitope modified vaccinia Ankara virus and a recombinant protein induce strong Th1 cell responses but fails to trigger neutralising antibodies required for protection

Ortiz, José Manuel Jaramillo; Paoletta, Martina Soledad; Gravisaco, Marí­a José; Arias, Ludmila Sol López; Montenegro, Valeria Noely; Fourniere, Sofía Ana María de la; Valenzano, Magalí Nicole; Guillemi, Eliana Carolina; Valentini, Beatriz; Echaide, Ignacio; Farber, Marisa Diana; Wilkowsky, Silvina Elizabeth

doi:10.1016/j.ttbdis.2019.101270

Cited by 10 publications

(10 citation statements)

References 45 publications

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“…Results in mice confirmed that adenoviruses, as well as the bacterially expressed multi-antigen, are highly reliable primer candidates, inducing high percentages of CD4 + and CD8 + T cells with a Th1 cytokine profile [82]. Subsequently, the same authors [83] used this subunit vaccine as a prime to immunize 13-15-month-old Holstein-Friesian steers with a modified vaccinia Ankara vector as a boost. Both prime and boost expressed a chimeric multi-antigen including the immunodominant B and T cell epitopes of the three aforementioned B. bovis proteins (MSA-2c, RAP-1 and hsp20).…”

Section: Babesia Sppmentioning

confidence: 83%

“…-IFN-γ expression in CD4 + T cells [66] Babesia spp. Rhoptry-Associated Protein (RAP-1) Antigen-specific IgG and IFN-γ release [72] Heat-shock protein 20 (Hsp 20) T cell proliferation and IFN-γ production [71] B. microti surface antigen (BMSA) Th17 and Th2 activation and IgG1 secretion [73] B. divergens Apical Membrane Antigen-1 (BdAMA-1) IgG1, IgG2, Th1 and Th2 activation [74] B. bovis rhoptry neck protein 2 (RON2) Induction of partially neutralizing antibodies that blocked the invasion process [79] Chimeric multi-antigen Antigen-specific IgG1, CD4 + and CD8 + IFN-γ + [81][82][83] Theileria parva Tp1-Tp2-Tp4-Tp5-Tp7-Tp8 CD8 + T-cell responses [92,[94][95][96][97][98][99][100][101] p67 Ab production [102] Polymorphyc immunodominant molecule (PIM) Production of Ab with neutralizing activity [103,104] p150 Ab production…”

Section: Rp778mentioning

confidence: 99%

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Immune Response to Tick-Borne Hemoparasites: Host Adaptive Immune Response Mechanisms as Potential Targets for Therapies and Vaccines

Torina

Blanda

Villari

et al. 2020

IJMS

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Tick-transmitted pathogens cause infectious diseases in both humans and animals. Different types of adaptive immune mechanisms could be induced in hosts by these microorganisms, triggered either directly by pathogen antigens or indirectly through soluble factors, such as cytokines and/or chemokines, secreted by host cells as response. Adaptive immunity effectors, such as antibody secretion and cytotoxic and/or T helper cell responses, are mainly involved in the late and long-lasting protective immune response. Proteins and/or epitopes derived from pathogens and tick vectors have been isolated and characterized for the immune response induced in different hosts. This review was focused on the interactions between tick-borne pathogenic hemoparasites and different host effector mechanisms of T- and/or B cell-mediated adaptive immunity, describing the efforts to define immunodominant proteins or epitopes for vaccine development and/or immunotherapeutic purposes. A better understanding of these mechanisms of host immunity could lead to the assessment of possible new immunotherapies for these pathogens as well as to the prediction of possible new candidate vaccine antigens.

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Section: Babesia Sppmentioning

confidence: 83%

Section: Rp778mentioning

confidence: 99%

Immune Response to Tick-Borne Hemoparasites: Host Adaptive Immune Response Mechanisms as Potential Targets for Therapies and Vaccines

Torina

Blanda

Villari

et al. 2020

IJMS

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“…Subunit vaccines avoid the problem of live vaccine-induced disease, and studies have looked at using recombinant proteins alone, as reviewed in [30], or recombinant proteins followed by a boost with a virus vector encoding the antigen [33] in order to stimulate protection against the clinical disease that is caused by B. bovis. Despite the stimulation of antigen-specific CD4+ T-cells and antibodies, none of the vaccine regimens resulted in protection from disease when the cattle were challenged with virulent B. bovis [30,33], illustrating the complexity of developing vaccines against B. bovis [6].…”

Section: Discussionmentioning

confidence: 99%

Immunization against a Conserved Surface Polysaccharide Stimulates Bovine Antibodies with Opsonic Killing Activity but Does Not Protect against Babesia bovis Challenge

et al. 2021

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Arthropod-borne apicomplexan pathogens remain a great concern and challenge for disease control in animals and humans. In order to prevent Babesia infection, the discovery of antigens that elicit protective immunity is essential to establish approaches to stop disease dissemination. In this study, we determined that poly-N-acetylglucosamine (PNAG) is conserved among tick-borne pathogens including B. bovis, B. bigemina, B. divergens, B. microti, and Babesia WA1. Calves immunized with synthetic ß-(1→6)-linked glucosamine oligosaccharides conjugated to tetanus toxoid (5GlcNH2-TT) developed antibodies with in vitro opsonophagocytic activity against Staphylococcus aureus. Sera from immunized calves reacted to B. bovis. These results suggest strong immune responses against PNAG. However, 5GlcNH2-TT-immunized bovines challenged with B. bovis developed acute babesiosis with the cytoadhesion of infected erythrocytes to brain capillary vessels. While this antigen elicited antibodies that did not prevent disease, we are continuing to explore other antigens that may mitigate these vector-borne diseases for the cattle industry.

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“…These include, among a few others, the rhoptry-associated protein-1 (RAP-1), two members of the variable major surface antigens (VMSA), the merozoite surface antigen-1 (MSA-1), and MSA-2c, the 12D3 antigen, and the heat-shock protein 20, either as whole recombinant proteins or selected B-and/or T-cell epitopes from them. Unfortunately, none of the formulations based on these antigens were able to elicit effective and strong protective immunity comparable to live vaccines in animal trials [48,[95][96][97]. The perceived collective experience indicates that the issues involved in vaccine development against bovine Babesia spp.…”

Section: Vaccines Against Bovine Babesiosismentioning

confidence: 99%

Pursuing effective vaccines against cattle diseases caused by apicomplexan protozoa

Florín-Christensen¹

2021

CABI Reviews

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Apicomplexan parasites are responsible for important livestock diseases that affect the production of much needed protein resources, and those transmissible to humans pose a public health risk. Vaccines, recognized as a cost-effective and environmentally friendly method for the prevention of infectious diseases in livestock, can avert losses in food production and decrease the exposure of humans to zoonotic pathogens. This review focuses on the need for and advances in vaccine development against the apicomplexan parasites Theileria spp., Babesia spp., Toxoplasma gondii, Neospora caninum, Eimeria spp., Besnoitia spp., Sarcocystis spp., and Cryptosporidium parvum. Together, the effect of these parasites on the cattle industry worldwide causes an enormous burden, yet they remain poorly controlled and very few effective and practical vaccines against them are available. Vaccine development is hampered by our scarce and limited knowledge of the biology and mechanisms of pathogenesis of these microorganisms, and the absence of correlates of host immune protection. More studies focused on these aspects as well as on the identification of parasite vulnerabilities that can be exploited for vaccine design are needed. Novel "omics" and gene editing approaches in understanding complex parasite biology together with advances in vaccinology will facilitate the development of effective, sustainable, and practical vaccines against cattle diseases caused by apicomplexan parasites. Such vaccines will help prevent animal and human diseases and allow production of enough animal protein to feed the growing human population in the twenty-first century and beyond.

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Immunisation of cattle against Babesia bovis combining a multi-epitope modified vaccinia Ankara virus and a recombinant protein induce strong Th1 cell responses but fails to trigger neutralising antibodies required for protection

Cited by 10 publications

References 45 publications

Immune Response to Tick-Borne Hemoparasites: Host Adaptive Immune Response Mechanisms as Potential Targets for Therapies and Vaccines

Immune Response to Tick-Borne Hemoparasites: Host Adaptive Immune Response Mechanisms as Potential Targets for Therapies and Vaccines

Immunization against a Conserved Surface Polysaccharide Stimulates Bovine Antibodies with Opsonic Killing Activity but Does Not Protect against Babesia bovis Challenge

Pursuing effective vaccines against cattle diseases caused by apicomplexan protozoa

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